Diagnosing Alzheimer's Dementia

Microscopic picture of the brain showing amyloid plaques and
 neurofibrillary tangles first seen by Alois Alzheimer in 1907

The diagnosis of Alzheimer's disease became headline news when the defence counsel of a prominent citizen of  Pune stated they were awaiting results of his brain MRI to finalise the diagnosis of dementia. Recently a patient's medication was stopped when his neuro-physician declared there were 'no plaques on MRI so it is not a case of Alzheimers'. The caregivers returned to me when his behaviour problems recurred.

Dementia including that of the Alzheimer's type is a clinical diagnosis (Grand 2011). Dementia is characterised by a triad of

1. Progressive deterioration of mental processes (cognitive abilities)
2. Behavioural and psychological symptoms of dementia (BPSD)
3. Difficulties carrying out day-to-day activities (activities of daily living or ADL).  

Alzheimer's Disease is commonest dementia after 65 years of age Alzheimer's dementia has an insidious onset, and progresses gradually and inexorably. This natural course is a key differentiator Alzheimer's from other forms of dementia. Dementia is suspected when a caregiver of an elderly person, or sometimes a person with a family history of dementia, becomes concerned about problems with memory. The diagnosis is purely clinical. No laboratory test or imaging (including MRI) is required to diagnose Alzheimer's disease. These investigations can only help differentiate the other forms of dementia when those are suspected.

Memory problems are a core feature of the disease. These manifest as

• Difficulty recalling details of recent events (forgets he has already dropped his grandchild to school), personal conversations, or specific elements of a task she is performing (eg, preparing a meal)
• Asking the same question multiple times while denying repeated questioning
• Tendency to make up events to fill memory gaps and to give inaccurate responses to questions (what he had for breakfast)

Other common cognitive concerns that could indicate dementia of the Alzheimer or any other type

• Disoreintation to time and place. As the illness progresses orientation worsens to include problems identifying familiar places, family members, or other well known people.
• Difficulties with activities of daily living (ADL). Problems with dressing or using common utensils
• Language impairments resulting in decreased conversational output, word-finding difficulties, and limited vocabulary.
• Visuo-spatial dysfunction manifest as impaired driving ability, and getting lost
• Problems with mathematical calculations impair ability to use money and balance finances.
• Impaired judgement in novel situations (difficulty planning a vacation).

Behavioural and psychological symptoms (BPSD)

• Depression occurs in up to 50% of individuals with Alzheimer's Dementia, and may be attributed to awareness of cognitive changes
• Lack of feeling or emotion (apathy) is associated with significant caregiver distress
• Psychosis generally occurs later in the disease course. Delusions are predominantly paranoid in nature, with fears of personal harm or mistreatment, theft of personal property (usually related to financial matters), and marital infidelity. Hallucinations are less common than delusions, and tend to be visual.
• Other behavioural symptoms include agitation, wandering, and sleep disturbances.

Diagnosis of Alzheimer's Disease is based on 

1. Detailed history to identify memory deficits, and other cognitive symptoms and assess their impact on the individual and family.
2. A thorough clinical exam (mental status examination) confirms the impairments in memory and cognition, and delineates the behavioural and psychiatric symptoms that cause caregivers concern. This usually includes using validated and standardised screening pencil and paper tests. 
3. Psychological testing confirms and quantifies the impairments across various areas of brain function (memory, language, visuo-spatial), assesses the treatment response, and documents progression of the illness with time.

Laboratory tests including MRI only differentiate Alzheimer's disease from other disorders such as subdural haematoma, brain tumour, hydrocephalus, and dementia associated with vascular disease. Magnetic Resonance Imaging (MRI) has no other clinical utility in Alzheimer's disease. These tests are not required or mandated by any classification system including that of the WHO (ICD) or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA).

Amyloid plaques, and neurofibrillary tangles are the hallmark of Alzheimer's disease and are required for a definitive diagnosis. These were first discovered by Alois Alzheimer in 1907.  His slides were rediscovered in 1992 and 1997. The rediscovered images show the classical pathological signs of the disease named after him. Amyloid plaques and neurofibrillary tangles are seen on microscopic examination of brain tissue using special staining techniques or by electron microscopy. Therefore the only way to obtain a definitive diagnosis of Alzheimer's disease is to obtain a brain tissue sample by biopsy or on autopsy. No MRI, however advanced can detect plaques.

For the purpose of treatment a probable diagnosis using bedside techniques of history and clinical examination is all that is required to diagnose Alzheimer's disease.

References

1. Dickerson BC. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimers Res Ther. 2010 Jul 6;2(4):21.
2. Graeber MB, Kösel S, Egensperger R, Banati RB, Müller U, Bise K, Hoff P, Möller HJ, Fujisawa K, Mehraein P. Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis. Neurogenetics. 1997 May;1(1):73-80.
3. Grand JH, Caspar S, Macdonald SW. Clinical features and multidisciplinary approaches to dementia care. J Multidiscip Healthc. 2011;4:125-47. Epub 2011 May 15.
4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44.

Parental supervision of children and adolescents

Parental supervision protects boisterous children from injury:
More time unsupervised corresponds to more injury 

“To my parents we were just two girls in the bedroom”. What exactly was going on? Without adequate supervision the parents of this teenager never found out; the memories returned to haunt her in adulthood. Studies comparing children with and without parental supervision show that lax parental supervision is associated with injury in toddlers and preschoolers; conduct problems in school going children; and road accidents, addictions, gambling and sexual risk taking in teenagers.

Parental supervision has three dimensions (Gitanjali 2004)

1. Attention - watching or listening 
2. Proximity - within or beyond reach 
3. Continuity - constant, intermittent, or not at all 

Two factors determine the degree to which a child would be left unsupervised (Morrongiello 2008)

1. Parent’s conscientiousness - the more conscientious the parent more the supervision
2. Child’s propensity for risky behaviour - the more impulsive and sensation seeking the child the more likely the child will be kept in direct view. 

Distinguishing adequate from neglectful supervision is not straight forward. The consequences of lower levels of supervision are not uniform for all children. The consequences depend to a great extent on child attributes. For children with high sensation seeking, even close supervision is not adequate to prevent injury. For children who are high in behavioural control, even not supervising does not elevate risk of injury.

Whether or not children comply with their parents’ requests to behave in safe ways is a complex interaction of parenting style, attachment style,  and child temperament. The level of supervision necessary to ensure a child’s safety should finally be based on the child’s characteristics. The only reliable maxim is that the time children could be safely left unsupervised generally increases with child age.

Parental supervision of an adolescent differs from supervising a younger child (DeVore 2005). Direct parental observation gradually gives way to indirect parental ‘‘monitoring’. This indirect supervision involves ongoing communication between parents and adolescents about the adolescents’

• Whereabouts
• Friends they are with
• Schedule to return home
• Contact information enabling parents to directly communicate with adolescents. 

Effective supervision entails active participation of the adolescent, and honest communication between adolescent and parents.

Parental monitoring buffers negative peer influence. Strong peer attachments and increasing independence from the family is a normal part of adolescent development. Unfortunately, youth whose peers engage in high-risk behaviour are at high risk for the development of similar behaviours. Not only are high levels of monitoring protective, low levels of parental monitoring have been associated with numerous risk behaviours.

More unsupervised time is associated with more sexual activity in youth (Cohen 2002). In one urban study more than half of sexually active youth had sex at home after school. For boys, sex and drug-related risks increase with amount of unsupervised time. Trust and communication did not predict decreases in problem behaviour as strongly as did monitoring. Parental monitoring may be particularly protective for high-risk young urban adolescents; those who spend a significant amount of non-school time unsupervised. 

References 

1. Cohen DA, Farley TA, Taylor SN, et al. When and where do youths have sex? The potential role of adult supervision. Pediatrics 2002; 110:e66 
2. DeVore ER, Ginsburg KR. The protective effects of good parenting on adolescents. Curr Opin Pediatr. 2005 Aug;17(4):460-5. 
3. Gitanjali S, Brenner R, Morrongiello BA, Haynie D, Rivera M, Cheng T. The role of supervision in child injury risk: Definition, conceptual, and measurement issues. Journal of Injury Control & Safety Promotion 2004;11(1):17-22. 
4. Morrongiello BA, Klemencic N, Corbett M. Interactions between child behavior patterns and parent supervision: Implications for children’s risk of unintentional injury. Child Development 2008;79(3):627-638.  

Treating Depression

Depressed mood or sadness lasting two weeks or more requires treatment. We all feel depressed, sad, or ‘blue’ occasionally. Moods and feelings change in response to events in our external environment. Usually depressive feelings or sadness last for a day or two; longer in case of loss or bereavement. However, if these feelings of sadness and hopelessness persist for more than 2 weeks and interfere with daily life, it indicates a clinical depression.

Depression is the fourth highest contributor to the global burden of disease. 

Clinical depression is a treatable illness. Many people never seek treatment due to lack of awareness, lack of access to mental health care, ignorance, or shame.

Signs and Symptoms

The hallmark of Clinical Depression is a pervasive depressed mood. This depressed mood is not responsive to positive events. There is associated slowness of thinking and movement; and there are thoughts related to guilt, self-blame, hopelessness and suicide . These features of constitute the classical triad of symptoms for the diagnosis of Clinical Depression. For a more formal diagnosis some or all of the symptoms below are used

1. Persistent sadness. Frequent crying, irritability, ‘emotional outbursts’
2. Slowing of movement and thoughts
3. Feelings of guilt - ‘I shouldn’t have done that’, ‘it is all my fault’
4. Worthlessness - ‘I haven’t achieved anything’, ‘I let my parents down’, ‘what I do has no value’
5. Hopelessness - ‘What’s the point?’, ‘I don’t see things getting better’
6. Thoughts of dying and suicide - ‘I would be better off dead’
7. Loss of interest in activities and hobbies that were once pleasurable
8. Difficulty concentrating, remembering details, making decisions
9. Insomnia, early morning wakefulness, excessive sleeping.
10. Change in appetite – appetite loss or overeating.
11. Fatigue, lethargy, decreased energy
12. Headache, cramps or digestive problems that are not relieved by treatment

How is depression treated?

The first step to treatment is to visit a psychiatrist. Your psychiatrist is the only mental health professional qualified to prescribe medication and provide psychotherapy. Your psychiatrist will take a detailed history of your symptoms, and will ask you to complete some questionnaires to assess their severity. He will also do a physical examination and may get some tests done (thyroid disorders and blood glucose related problems can cause similar symptoms).

The treatment of depression rests on two pillars

1. Pharmacotherapy (medication)
2. Psychotherapy (counselling, CBT)

Medication (pharmacotherapy) is required for moderate and severe depressions. Formal psychotherapy is started later once concentration and thinking improve. Your psychiatrist will prescribe an appropriate antidepressant. Antidepressants are not addicting. Side effects if any occur during the initial phase of treatment, they should not make you feel worse. Antidepressants must be taken for 4-6 weeks before they have a full effect. Later you should continue the medication even if you are feeling better to prevent a relapse. Suddenly stopping antidepressants can precipitate a relapse. Medication should be tapered gradually under your doctor’s supervision. If you follow your doctor's advice regarding follow up visits your treatment will be optimal.

Psychotherapy alone may be used in mild depression. Usually it is combined with medication for moderate and severe depressions. Psychotherapy is of two types:

1. Cognitive Behaviour Therapy (CBT) identifies self-defeating, ‘negative thoughts’ and behaviours that perpetuate clinical depression in a vicious cycle. Your therapist then works with you to replace these thoughts and behaviours with ‘positive’ ones to help you recover from the illness.
2. Interpersonal Therapy (IPT) helps people understand and work through troubled relationships that may be at the root of depression or making it worse.

How can I help a friend or family member who is depressed?

1. Listen carefully.
2. Offer support, understanding and encouragement.
3. Never dismiss feelings, but point out realities and offer hope.
4. Encourage them to go out for walks, outings and other simple activities. Don’t push too hard but keep trying.
5. Make sure they keep appointments with the psychiatrist and stay in therapy.
6. Never ignore suicide comments
• Gently correct blatantly ‘negative’ thoughts. Help the person form an action plan to resolve the problem
• DON'T LEAVE THEM ALONE until they OK the plan. 
• Accompany them to a known responsible person or a doctor or mental health professional. You could save a life.

What can I do when I am depressed?

1. Stay active. Exercise; go out for a movie, or any event you previously enjoyed.
2. Eat regular meals. Don’t skip them even if you are not hungry.
3. Go to bed at a regular time. Don’t wait until you are extremely tired so you can get sleep. Insomnia is the first symptom to respond to antidepressant medication
4. Set realistic goals for yourself.
5. Break up large tasks into smaller ones and do what you can.
6. Spend time with others, confide in a trusted friend or relative.
7. Postpone important decisions such as getting married/divorced, changing jobs until you are feeling better.
8. Do not wait too long to get treatment.
9. Expect your mood to improve gradually. Sleep and appetite will improve before your mood changes.
10. Keep your appointments with your psychiatrist and do not stop your medication suddenly.

Reference

Rejection and aggression - the fury of the scorned male

Rejection experienced in an intimate relationship can trigger unexpected aggression with sometimes fatal consequences. A working woman in Pune was stabbed to death in her home when she spurned the marriage proposal of a good friend. Another 17 year-old girl from Hadapsar was stabbed in the stomach for rebuffing the overtures of a relative. Why would a man assault a woman after professing his love to her? Many instances of aggression arise from events where an individual perceives he is not sufficiently loved or valued in the context of an intimate relationship.

People differ in their readiness to perceive and react to rejection. The desire to belong is a basic human need. Some maintain equanimity while others over-react in ways that harm their relationships and their well-being. Hostility and aggression are among the most destructive reactions to rejection. Low self-esteem, depression, jealousy, self-neglect and a breakdown of daily routine are other painful outcomes of being rejected. Social rejection is the strongest predictor of violence in adolescents (Surgeon General 2001). This association between rejection and aggression is also repeatedly shown in social experiments.

Rejection triggers behaviours internalised during interactions with parents during infancy and early childhood. Based on these interactions children form certain expectations regarding the satisfaction or rejection of their needs. When childhood needs are met sensitively and consistently the child forms secure expectations. When childhood needs are met with rejection the child forms a pattern of insecure expectations involving doubts and anxieties. These repeated early interactions determine the individuals attachment style - the communication pattern exhibited in close relationships.

Aggression is first learned during infancy as a response to separation from the mother. The purpose is to reunite with the mother and discourage future separation. Adults who are socially immature respond to separation from a loved one with shouting, crying, and throwing or smashing objects. Again the purpose is to protect the relationship. Men with a fearful or preoccupied attachment style are more likely to be jealous, violent and abusive in intimate relationships. This tendency to violence increases when the relationship is threatened. Males with a fearful attachment style are anxious about gaining their partners approval and at the same time are fearful of being rejected by them. These males are more likely to attribute negative intent to their partners. This combination of internal conflict and external blame makes men with a fearful attachment style respond to rejection with aggression (Leary 2006).

Jealousy is the precursor of aggression in many close relationships. Jealousy occurs when people believe that another person does not sufficiently value their relationship because of the presence or intrusion of a third party. Men who are abusive have higher interpersonal jealousy. Abused women and the men who abuse them report jealousy as the most common precursor to violence. Among both men and women, intimate violence is often provoked by real or imagined infidelity (Leary 2006). We have already discussed jealousy in the context of the family.

Rejection-sensitivity is a personality characteristic associated with aggression elicited by rejection in love and romance. People high in rejection sensitivity (Downey 1996)

1. Anxiously expect rejection by significant people in their lives.
2. Readily perceive intentional rejection in the ambiguous or insensitive behaviour of their new partner.
3. Over-react to rejection

Gender differences (Downey 1996) dictate that men with high rejection sensitivity manifest jealousy in the face of perceived rejection. Their consequent attempts to control their love object’s interactions with other males leads to further dissatisfaction in the relationship. When they are not successful in this they respond with rage - the common fallout of jealousy. Females react to perceived rejection with hostility and withdrawal of support. Both gender reactions lead to dissatisfaction with the partner and subsequent breakup of the relationship. If taken to an extreme, the jealousy in the rejection sensitive male can lead to fatal consequences for object of his affections.

Despite these negative experiences rejection sensitive people are repeatedly drawn to intimate relationships. The new relationship is viewed as an opportunity for acceptance. Initially they work hard to ingratiate themselves with their partner. However, the inevitable transient negativity, insensitivity, or preoccupation triggers the deeply ingrained anxieties and expectations of rejection. The person over-reacts to minor and ambiguous signals from the love object and starts the cycle of dissatisfaction in the relationship.

Rejection sensitivity is deeply ingrained in the personality. An intimate partner or a therapist can alter the expectancies and anxieties about rejection. It is possible for the rejection sensitive person to develop better conflict resolution skills. But only when there is a high degree of motivation in the rejection-sensitive person and a skilled, and nurturing partner.

References

1. Özlem Ayduk, Anett Gyurak, and Anna Luerssen. Individual differences in the rejection-aggression link in the hot sauce paradigm: The case of Rejection Sensitivity. J Exp Soc Psychol. 2008 May 1; 44(3): 775–782. doi: 10.1016/j.jesp.2007.07.004
2. Downey G, Feldman SI. Implications of rejection sensitivity for intimate relationships. J Pers Soc Psychol. 1996 Jun;70(6):1327-43.
3. Leary MR, Twenge JM, Quinlivan E. Interpersonal rejection as a determinant of anger and aggression. Pers Soc Psychol Rev. 2006;10(2):111-32.
4. Office of the Surgeon General. (2001). Youth violence: A report of the Surgeon General. U.S. Department of Health and Human Services. 

Brain effects of cellular phone use

Mobile phone induced EEG changes

Cellular phones affect the brain to cause injury and death through inattention and reaction time delays. Cellular phone radiations also induce abnormal changes in brainwaves. Here we are not concerned with the potential for death due to the cancer generating properties of GSM radiation. We are concerned with the direct and immediate adverse effects of cellular phone conversations.

Cellphones continue to kill their users in Pune. At least two people died crossing the Hadapsar railway tracks while engrossed in conversation. One of them was oblivious to shouting onlookers warning him of the oncoming train. Another cell-bewitched user fell off his eighth-floor balcony while conversing. And of course cellphone use while driving continues to kill despite the ban. All this is besides the cancer risk that the WHO (2011) is unable to disregard.

How distracting is a cellphone conversation?

Any extraneous demand on attention will distract from performance on an ongoing task. If the task itself is critical, as in driving, distractions can be lethal. Even hands-free cellphone conversations while driving cause attention lapses and slow down reaction time (McCartt 2006). These effects are seen in drivers across gender and age groups. The surest way to verify that a crash occurred during mobile phone use is to check billing records. Using this method crashes leading to personal or property damage are found to be four times more common during mobile phone use. When there is a higher mental load in the mobile phone conversation problems with attention and reaction time are magnified (Lin 2006).

The stream of media reported mobile phone related deaths during the performance of everyday tasks highlights the much neglected aspect of non-driving related mobile phone injuries. Pedestrians conversing on a mobile phone cross the road more slowly, are less likely to look for traffic, and take more risks in the face of oncoming traffic (Neider 2010). Pedestrians are less likely to cross a road successfully while using a mobile phone than while listening to music on an iPod. These effects are more pronounced in adolescents.

The risk of injury is related to the need to shift the focus attention from the task on hand to the conversation. Conversing on a mobile phone takes up a significant amount of mental processing ability. Mobile phone conversations increase reaction times and reduce accuracy on task performance. These impairments increase with increasing complexity of the task being interrupted. One can only imagine the effect of a mobile phone interruption on the outcome of an ongoing medical procedure.

Do cellular phone generated electromagnetic waves interfere with brainwaves?

Intriguingly, GSM microwave radiation interacts with and distorts brainwaves. This effect can be directly measured and recorded on an electro-encephalogram (EEG). Electromagnetic fields emitted by cellular phones cause a slowing of brain waves (delta waves) that is not seen in healthy adults during normal wakefulness. These changes persist for up to ten of minutes after the mobile phone is switched off. Children are more vulnerable to these effects as microwave absorption is greatest in an object the size of a child’s head. This radiation also penetrates the thinner skull of an infant with greater ease (Kramarenko 2003).

Brainwaves normally discharge asynchronously when attention is drawn to an event in the environment. This event related de-synchronisation is altered by mobile phone electromagnetic fields. This affects tasks involving memory, especially in children (Krause 2000, 2006). Cellphone radiofrequency waves have a dose dependent effect on tasks attention, concentration and short term memory. Reaction speed decelerates with increasing GSM field intensity. These effects are more pronounced when the responding hand and side of radiation exposure are taken into account (Luria 2009).

These dose dependent radiation effects are also seen when cellular phone use also alters brainwave patterns (spindle activity) during slow-wave sleep. These effects are long lasting, and indicate a non-thermal effect. The thalamus, a part of the brain that processes sensation, is responsible for generating sleep spindle activity and may be especially susceptible to cellphone radiation (Regel 2007).

Walk and talk is a bad idea

References

1. Robert Baan, Yann Grosse, Béatrice Lauby-Secretan, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Farhad Islami, Laurent Galichet, Kurt Straif, on behalf of the WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of radiofrequency electromagnetic fields. The Lancet Oncology, Volume 12, Issue 7, Pages 624 - 626, July 2011 doi:10.1016/S1470-2045(11)70147-4
2. Kemker BE, Stierwalt JA, LaPointe LL, Heald GR. Effects of a cell phone conversation on cognitive processing performances. J Am Acad Audiol. 2009 Oct;20(9):582-8.
3. Kramarenko AV, Tan U. Effects of high-frequency electromagnetic fields on human EEG: A brain mapping study. Intern. J. Neuroscience, 113:1007–1019, 2003 DOI: 10.1080/00207450390220330
4. Krause CM, Sillanmäki L, Koivisto M, Häggqvist A, Saarela C, Revonsuo A, Laine M, Hämäläinen H.  Effects of electromagnetic fields emitted by cellular phones on the electroencephalogram during a visual working memory task. Int J Radiat Biol. 2000 Dec;76(12):1659-67.
5. Krause CM, Björnberg CH, Pesonen M, Hulten A, Liesivuori T, Koivisto M, Revonsuo A, Laine M, Hämäläinen H. Mobile phone effects on children's event-related oscillatory EEG during an auditory memory task. Int J Radiat Biol. 2006 Jun;82(6):443-50.
6. Lin CJ, Chen HJ. Verbal and cognitive distractors in driving performance while using hands-free phones. Percept Mot Skills. 2006 Dec;103(3):803-10.
7. Luria R, Eliyahu I, Hareuveny R, Margaliot M, Meiran N. Cognitive effects of radiation emitted by cellular phones: the influence of exposure side and time. Bioelectromagnetics. 2009 Apr;30(3):198-204.
8. McCartt AT, Hellinga LA, Bratiman KA. Cell phones and driving: review of research. Traffic Inj Prev. 2006 Jun;7(2):89-106.
9. Mark B. Neider, Jason S. McCarley, James A. Crowell, Henry Kaczmarski, Arthur F. Kramer. Pedestrians, vehicles, and cell phones. Accident Analysis and Prevention 42 (2010) 589–594
10. Regel SJ, Tinguely G, Schuderer J, Adam M, Kuster N, Landolt HP, Achermann P. Pulsed radio-frequency electromagnetic fields: dose-dependent effects on sleep, the sleep EEG and cognitive performance. J Sleep Res. 2007 Sep;16(3):253-8.